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it successful, it can be envisioned that KP-1461 would be given together with an anti-viral regimen such as Atripla and after a year or so, the viruses could be mutated out of existence and patients could achieve a cure.The magnitude of disruption from such a technology to the current $12B HIV market would be drastic and completely game changing.http://www.koronispharma.com/pdf/110126%20Wedbush%20Report%20(Re-%20Gilead-Koronis).pdf

I get the impression that if little Koronis was working on yet another long-term therapy, Gilead would be going after merger (if anything), but this is something they would like to "stifle" (their word).

My guess is, if Gilead felt threatened by Koronis, they would buy the rights to the technology, put it in a box and close the lid... for a long time. Given the less than stellar results from the Koronis studies, Gilead could merely state that additional in-house investigation raised doubts about efficacy and the company has terminated research of KP-1461... simple as that.

If Gilead thought it did work, it would be an ace in their hand, to be ressurected when a credible threat emerged from a competitor. Remember, commercial companies are in business to maximize profit. Their fudiciary responsibility is to their shareholders, not their patients.

This is why public and non-profit funding (like the Gates foundation and Hughes Medical) is so important. They help keep the rest of the industry ethical.

I get the impression that if little Koronis was working on yet another long-term therapy, Gilead would be going after merger (if anything), but this is something they would like to "stifle" (their word).

Accord to this information some big companies, love stifling competition:

You know what the worst is.. is when people tell me there IS already a cure.. but the pharmcompanies don't want to let it out.. I have a hard time believing this. It would get out for sure. But it makes me nervous that so many people are convinced of this. I'm not one for conspiracy theories.. and obviously a cure is very important to me. It seems like they're just one small breakthrough away from it... but it's very elusive *_*

i hear the same thing for cancer too. i put that in the back of my mind and hope that ethics and stuff like that really are in the forfront and that no one could have a cure for these heinous diseases and not let us have them. maybe im naive.

You know what the worst is.. is when people tell me there IS already a cure.. but the pharmcompanies don't want to let it out.. I have a hard time believing this. It would get out for sure. But it makes me nervous that so many people are convinced of this. I'm not one for conspiracy theories.. and obviously a cure is very important to me. It seems like they're just one small breakthrough away from it... but it's very elusive *_*

I don't see how these companies would be able to keep a cure a secret, with the number of people who are involved in the research. Also, I think while there is a ton of money to be made in the treatment, a cure could also be big bucks because of the numbers of people who have it. Also, you'd probably still have people contracting the virus for many many years. The first company to come up with the cure would completely shut down all the others, so they may still have an incentive to do the right thing.

They f**king better do the right thing...and there is major money to be made and on top of it the prestige and notoriety that comes with it..and those that would even think about stifling the possibility should be ashamed...

4 years later and Timothy Brown still aint got no HIV! It can definitely happen to us. Only time will tell.

Things will only get better as time goes on. It went from people dying like crazy with HIV.....to taking 20+ pills a day to stay alive...... to taking like 10 pills a day...... to a just a few a day....... and now some people take just as little as one a day. Side effects went from super nasty... to mostly tolerable (depending on the med of course).

Whats the next step? Once a week pill? Once a month? A quarterly/semi-annually/annual vaccine like a flu shot? Or even better....Eradication! Who knows? Only time will tell but I'm optimistic things will change soon. I don't talk like this usually. I'm usually the one to complain but lately Ive been doing a lot of thinking.... and things could be worse, but its not. Thank god.

I do hope ur right...but back to the thread, what is currently going on with KP1461? Are theytrying to raise money for another trial? Would any human participate in this? I mean this is some heavy duty shit but it could be lead to the C word...right now im hoping for this, Sangamo, and still hoping for Dr. sudhir Paul...the race continues I just wish thy would go faster and I know I've not had this long but even being poz for a day is long enough...

My take is that if a company like GILD that's already making a TON of $$$ from HIV were to sense a real threat, it wouldn't be that they "hide" a cure... they could acquire it and drastically slow down the already slow path to learning if it really works.

I truly doubt if a cure was proven, that it would be kept from the public... too many people involved in trials would know about it to keep it a secret.

In any case reading carefully the article of Wedbush it seems that analysts are recommending Gilead to concentrate future investments in other areas like HCV and IPF in consideration of a likely HIV franchise cliff that Gilead could face in the next years.

« Last Edit: April 06, 2011, 10:56:14 PM by xman »

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sign the petition launched by the aids policy project addressed to the nih aimed to increase the money needed to find the cure:

Given the recent drug price increases effected by Gilead, they seem to be anticipating an end to the HIV gravy train. True to their fudiciary duty to the shareholders, they are trying to get as much $$$ out of their HIV franchise while they still can. They could expect any or all of the following; a cure, therapeutic long-term treatment, or less costly generics as patents expire.

The most recent financing will be used to conduct Phase II clinical trials. If the trials are successful, Elmer said the company will make a determination whether to partner with a larger pharmaceutical company or to continue going alone with later-stage research.

Of course as a venture capitalist, Elmer knows that multiple problems can arise for an early stage drug company. And that's part of the reason he is trying to guard his optimism.

"We are feeling pretty good about it right now, but we will have to wait and see," he said.

Several series of in vitro experiments were done in cell cultures, using a very nasty strain of HIV, a homogeneous, highly fit virus. And after an average 15 serial passages, that virus was irreversibly extinguished--repeatedly. Repeated, published experiments have demonstrated that you can collapse the viral population with KP-1461.

It is my belief that most drug companies are starting to realize that a cure for HIV is an inevitability and is only a matter of time. The Berlin patient is proof that a cure which was once thought unattainable is a reachable reality. Granted we won't be using the same technique but it is evidence that the virus can at least be eliminated. And like John says if they can be the one to do it first then they will reap a big PR coup not to mention licensing the drug.

- KP-1461 repeatedly caused a permanent eradication of HIV in vitro- No evidences of drug resistances to KP-1461- KP-1461 is safe and well tolerated over 80 patients in these early human clinical trials- Conclusive evidences that KP-1461 cause a significantly increase rate of mutations formations in HIV in early human clinical trials

And that's what has been observed in the clinical trials participants (3 class drugs resistant at entry):no cure, but a significant increase rate of mutations formations in HIV (124 days trial)

Koronis need now a sophisticated development partner to complete late stage development (full-scale phase II, one or more phase III for regulatory approval)

Now, Koronis draws funding ($20 million to be used for studies) so the second Phase II can start.

This second Phase II have to answer to the following questions:

1. Is KP-1461 able to produce a meaningful reduction in VL?2. What kind of optimized treatment we will need to get this VL drop?

It's during this new phase II that they will be able to conclude whether or not KP-1461 might or not lead to a cure, be use as a new treatment option, or can be forgotten.

If successful, then the Phase III can start. It will have to compare KP-1461 results against other standard available treatments.

Still a long way to go. The only things we can enjoy now, is the results we already get plus hopes.

- KP-1461 repeatedly caused a permanent eradication of HIV in vitro- No evidences of drug resistances to KP-1461- KP-1461 is safe and well tolerated over 80 patients in these early human clinical trials- Conclusive evidences that KP-1461 cause a significantly increase rate of mutations formations in HIV in early human clinical trials

And that's what has been observed in the clinical trials participants (3 class drugs resistant at entry):no cure, but a significant increase rate of mutations formations in HIV (124 days trial)

Koronis need now a sophisticated development partner to complete late stage development (full-scale phase II, one or more phase III for regulatory approval)

Now, Koronis draws funding ($20 million to be used for studies) so the second Phase II can start.

This second Phase II have to answer to the following questions:

1. Is KP-1461 able to produce a meaningful reduction in VL?2. What kind of optimized treatment we will need to get this VL drop?

It's during this new phase II that they will be able to conclude whether or not KP-1461 might or not lead to a cure, be use as a new treatment option, or can be forgotten.

If successful, then the Phase III can start. It will have to compare KP-1461 results against other standard available treatments.

Still a long way to go. The only things we can enjoy now, is the results we already get plus hopes.

Cheers John,

Definetely agree we can all be hopefull about this. Something worth following for sure. I probably would try to get in the trial if I was in the states. Because that's not possible I'd like to thank all those who will be doing the trials for all our benefit, and of course all those who have done so in the past.

Phase 2a TrialAn Open-label, Multicenter, Mechanism Validation Study to Evaluate the Safety, Efficacy, and Tolerability of KP-1461 as Monotherapy for 124 Days in ARV-experienced, HIV-1-infected Subjects. This study enrolled 27 of the 32 subjects targeted for the trial. Koronis stopped this trial prior to complete enrollment in order to conduct in vitro serial passage studies, which have confirmed HIV ablation consistent with original preclinical results. The trial closure was not requested or required by the FDA and was not related to any safety concerns or adverse events during the trial. KP-1461 was shown to be well tolerated. Results also demonstrated drug activity as subjects treated with KP-1461 had an increased frequency of HIV mutations that were statistically significant as compared to a separate control group.

It seems that the Phase 2a trial has been suspended, though I don't really understand why. In fact, I can't tell if this is a good thing or a bad thing. Could someone clarify, please? Thanks!

As I remember it, there was some issue with Koronis not being able to repeat their earlier in vitro results. So they went back and re-ran their tests. Looks like the got a result similar to their first results -- good news.

As I remember it, there was some issue with Koronis not being able to repeat their earlier in vitro results. So they went back and re-ran their tests. Looks like the got a result similar to their first results -- good news.

Ah, that's very good news. Thanks for the clarification. I'm afraid I'm not so well versed with medical speak. Keeping fingers crossed!

The concept behind KP-1461 is so basic, I bet the people that developed it slapped their foreheads and exclaimed "Of course, this is so simple!"

The premise is that it encourages the HIV virus to continually and rapidly mutate in random ways, making it worthless in that it cannot reproduce or infect. From what I understood of the Phase II clinical trials, patients were given KP-1461 and Atripla for a year - KP-1461 to damage the viruses already in the system and Atripla to keep the viruses from reproducing as much as possible.

(Syracuse, NY. – April 28, 2010) – Rondaxe Enterprises, LLC, announced today that it has entered into an agreement with Koronis Pharmaceuticals to secure a commercialization partner to advance an HIV drug known as KP-1461. KP-1461 is currently in phase II clinical trials and is demonstrating remarkable potential to alter the treatment paradigm for HIV.

“If approved, KP-1461 could significantly advance the treatment of HIV over currently available agents, and lead to a cure, rather than today’s chronic treatment of the disease,” said Rondaxe’s James Bergey, Ph.D., who is leading the project. ...

I would really like to understand how KP-1461 deals with the virus in the reservoirs. It seems to me that unless there is a specific mechanism of action that allows the drug to reach the reservoirs, that the virus in these reservoirs would remain untouched and unmutated. In that case, I guess KP-1461 would just be another med, albeit one that the virus cannot develop resistance to (which would be a wonderful improvement).

From what I understand, KP-1461 is used in combination with another treatment like Atripla, Btripla or the combination therapies out there. Atripla to reduce the viral load, and KP-1461 to damage the viruses themselves by causing them to mutate excessively. Basically, this combination situation causes the viruses in the reservoirs to be released, thereby be vulnerable to KP-1461 and the other meds.

I wouldn't be getting to optimistic here. Great that it can cause highly mutated strains of the virus that is actually replicating, but what about the virus that isn't? The main problem with being able to eradicate HIV are the latent cells that it can hide out in. How is taking a medication that can encourage mutations getting HIV out of these cells? Also, wouldn't all these mutations make it even more possible to become resistant to other drugs that you might otherwise be taking to control the virus? So I'd be very cautious before being sold on an idea such as this. Yes, it would work nicely in a system with no latent cells, sure. But unfortunately, that's not reality with HIV. I guess if all you have in your body is a strain that is already resistant to most drugs out there, taking this would be a great option. But I don't see it as a cure unless I'm missing something.

I'm more encouraged by other ideas being researched, such as gene therapy with HIV-resistant CD4's and stem cells, or vaccines that can train the immune system to fight off the virus without the need for medications.

I would really like to understand how KP-1461 deals with the virus in the reservoirs. It seems to me that unless there is a specific mechanism of action that allows the drug to reach the reservoirs, that the virus in these reservoirs would remain untouched and unmutated. In that case, I guess KP-1461 would just be another med, albeit one that the virus cannot develop resistance to (which would be a wonderful improvement).

This is an excellent point. After an in-depth conversation with some of the Koronis folks, I'm no closer to understanding how KP-1461 will somehow achieve either a sterilizing or or functional cure, nor am I understanding any of the potential clinical benefits of this agent. The public relations surround this drug appears much more solid than the science. While I understand that PR and resulting press is necessary to spark investment needed to conducted additional Phase II studies looking at clinical efficacy -- which thus far hasn't been demonstrated (a high mutation rate hasn't been proven to be a surrogate marker of anything) -- simply because the word "cure" makes its way into media reports doesn't necessarily make it so.

Once there's proof of concept, we'll all have a lot more to talk about. But we're not there yet, period.

As the VP Manufacturing & Business Development at Koronis, I wanted to respond to the number of questions/comments on this forum concerning KP-1461’s impact on the virus in the latent reservoirs.

KP-1461 is effective against viruses which are actively replicating. Therefore, if latent reservoirs of virus are activated, this will also enable KP-1461 to be incorporated into these viral genomes and cause progressively deleterious mutations. While the effect of these mutations is not immediate, it stands to reason that successive cycles of reservoir activation in the presence of a VDA agent will result in progressively weakened viruses seeding subsequent reservoirs until the weakened virus is no longer able to elicit a productive infection. Therefore, we believe that use of KP-1461 in conjunction with a compound that activates the latent reservoir could eventually provide a sustained virologic response.

In closing, it is important to note that although there is considerable promise with this therapeutic approach, more studies are required to validate the true potential of VDA and KP-1461 in humans. With this in mind, we are very encouraged by the recently published data from our first Phase 2 study and are actively moving forward with plans for our next study to further evaluate the clinical potential of KP-1461.

As the VP Manufacturing & Business Development at Koronis, I wanted to respond to the number of questions/comments on this forum concerning KP-1461’s impact on the virus in the latent reservoirs.

KP-1461 is effective against viruses which are actively replicating. Therefore, if latent reservoirs of virus are activated, this will also enable KP-1461 to be incorporated into these viral genomes and cause progressively deleterious mutations. While the effect of these mutations is not immediate, it stands to reason that successive cycles of reservoir activation in the presence of a VDA agent will result in progressively weakened viruses seeding subsequent reservoirs until the weakened virus is no longer able to elicit a productive infection. Therefore, we believe that use of KP-1461 in conjunction with a compound that activates the latent reservoir could eventually provide a sustained virologic response.

In closing, it is important to note that although there is considerable promise with this therapeutic approach, more studies are required to validate the true potential of VDA and KP-1461 in humans. With this in mind, we are very encouraged by the recently published data from our first Phase 2 study and are actively moving forward with plans for our next study to further evaluate the clinical potential of KP-1461.

Hello Mr. Fromhold:Thank you for posting this information - it sounds very encouraging. I'm not sure if a missed it or not, but are there thoughts as to how to activate the latent reservoirs, or would this occur as a result of depleting the non-latent active reservoirs. Also, in regards to response time for the successive cycles to be activated and eliminated - is there any idea of how long that would take and/or how long the treatment would need to be to completely eradicate the virus, including the latent resorvoirs from the body?

As the VP Manufacturing & Business Development at Koronis, I wanted to respond to the number of questions/comments on this forum concerning KP-1461’s impact on the virus in the latent reservoirs.

KP-1461 is effective against viruses which are actively replicating. Therefore, if latent reservoirs of virus are activated, this will also enable KP-1461 to be incorporated into these viral genomes and cause progressively deleterious mutations. While the effect of these mutations is not immediate, it stands to reason that successive cycles of reservoir activation in the presence of a VDA agent will result in progressively weakened viruses seeding subsequent reservoirs until the weakened virus is no longer able to elicit a productive infection. Therefore, we believe that use of KP-1461 in conjunction with a compound that activates the latent reservoir could eventually provide a sustained virologic response.

In closing, it is important to note that although there is considerable promise with this therapeutic approach, more studies are required to validate the true potential of VDA and KP-1461 in humans. With this in mind, we are very encouraged by the recently published data from our first Phase 2 study and are actively moving forward with plans for our next study to further evaluate the clinical potential of KP-1461.

I was under the impression that if we could activate the viral reservoirs then currently existing HAART would do a fine job of destroying the virus. Is that not the case?

Obviously all progress towards a cure is welcomed and I am confidentent a "funtional" cure could come about in the next 5 years (at least in the west)However as we all now there is a masive sigma with this illness that exists in no other and untiil they can STOP 100% the spread of the disease, so that you can not pass on the virus (in sex at least) the sigma will continue and QoL will continue to be low